Septo-optic Dysplasia

Septo-optic dysplasia, also known as De Morsier syndrome, is a rare congenital disorder that affects 1 in 10,000 live births (1). This condition is defined by the co-occurrence of at least two of the following three diagnostic features: optic nerve hypoplasia, pituitary hypoplasia, and septal leaflet anomaly.

SOD is suspected in cases of partial or complete absence of the septum pellucidum leaflets, especially in cases of agenesis of the septum pellucidum (ASP), which is a brain malformation with an incidence of 2-3/100,000 in the general population. (2)

1. Long-term postnatal outcome of fetuses with prenatally suspected septo-optic dysplasia S. SHINAR1, S. BLASER2, D. CHITAYAT3,4, T. SELVANATHAN5, V. CHAU5, P. SHANNON6, S. AGRAWAL1, G. RYAN1, V. PRUTHI1, S. P. MILLER5, P. KRISHNAN2 and T. VAN MIEGHEM Ultrasound Obstet Gynecol 2020; 56: 371–377
1Ontario Fetal Centre, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada; 2Department of Diagnostic Imaging, Hospital for Sick Children, Department of Medical Imaging, University of Toronto, Toronto, ON, Canada; 3Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada; 4Division of Clinical and Metabolic Genetics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada; 5Department of Pediatrics, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada; 6Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada

2. Neuro-Ophthalmological Manifestations Of Septo-Optic Dysplasia: Current Perspectives Mario Ganau, Sibel Huet, Nikolaos Syrmos, Marco Meloni, Jayaratnam Jayamohan Eye Brain. 2019; 11: 37–47.  Published online 2019 Oct 18
 

3. Septo-optic dysplasia plus: a spectrum of malformations of cortical development S P Miller 1, M I Shevell, Y Patenaude, C Poulin, A M O'Gorman Neurology 2000 Apr 25;54(8):1701-3. 

4. Role of three-dimensional ultrasound measurement of the optic tract in fetuses with agenesis of the septum pellucidum
J. P. BAULT*†‡, L. J. SALOMON†‡, L. GUIBAUD§ and R. ACHIRON¶Ultrasound Obstet Gynecol 2011 ; 37 : 570–575 *Centre d’Echographies Ambroise Pare Les Mureaux, CHI Poissy Saint-Germain, Yvelines, France; †Maternité Necker-Enfants Malades, PHP, Université Paris Descartes, Paris, France; ‡SFAPE: Société Pour l’Amélioration des Pratiques en Echographie, Paris, France;§Imagerie Pédiatrique et Fœtale, Hˆ hôpital Femme Mère Enfant, Université Claude Bernard Lyon I, Lyon Bron, France; ¶Department of Obstetrics and Gynecology, Sheba Medical Center, Sackler Scholl of Medicine, Tel Aviv University, Tel Aviv, Israël

5. Prenatal diagnosis and outcome of fetuses with isolated agenesis of septum pellucidum: cohort study andmeta-analysis E. DI PASQUO1, M. KULEVA2,3, C. ARTHUIS3, G. MORGANELLI1,4, F. ORMITTI5, A.-E. MILLISCHER6, D. GREVENT6, Y. VILLE3, T. GHI1,4# and L. J. SALOMON3# Ultrasound Obstet Gynecol 2022; 59: 153–161
1Department of Obstetrics and Gynecology, University Hospital of Parma, Parma, Italy; 2Department of Obstetrics, Hopital Intercommunal de Montreuil, Montreuil, France; 3Department of Obstetrics and Fetal Medicine, Hopital Necker-Enfants Malades, Assistance Publique-Hopitaux de Paris, Paris Descartes University, Paris, France; 4Department of Medicine and Surgery, Obstetrics and Gynecology Unit, University of Parma, Parma, Italy; 5Department of Radiology, University Hospital of Parma, Parma, Italy; 6Departmentof Pediatric Radiology, Hopital Necker-Enfants Malades, APHP, Universite Paris Descartes, Paris, France

6. Septo-optic dysplasia Emma A Webb1 and  Mehul T Dattani1,Eur J Hum Genet. 2010 Apr; 18(4): 393–397. 

7. The ratio of cavum septi pellucidi width to anteroposterior cerebellar diameter: A novel index as a diagnostic adjunct for prenatal diagnosis of trisomy 18 He, Miao, Du, Liu, Xie, Hongning, Lei, Ting, Zheng, Qiao, Wu, Lihong Journal of Obstetrics and Gynaecology Research 1447-0756 / 1341-8076

8. Visualization of the fetal optic chiasma using three-dimensional ultrasound imaging. BAULT JP. Ultrasound Obstet Gynecol
2006; 28: 862–864.
 
9. P38.13: fetal optic chiasm measurements: reference range at 22–36 weeks of gestation. BAULT JP, SALOMON LJ. Ultrasound Obstet
Gynecol 2007; 30: 596.
 
10. Fetal optic chiasm measurements: a simpler way! J.Bault Ultrasound in Obstetrics & Gynecology 2016;48(Suppl. 1): 51 – 166.

11. Assessment of fetal optic chiasm: an echo anatomic and reproducibility study. PALADINI*, R. BIRNBAUM*, G. DONARINI*, I. MAFFEO* and E. FULCHERI† Ultrasound Obstet Gynecol 2016; 48: 727–732*Fetal Medicine and Surgery Unit, Istituto G. Gaslini, Genoa, Italy; †Fetopathology Unit, Istituto G. Gaslini, Genoa, Italy
 
12. Two-dimensional visualization and measurement of the fetal optic chiasm: improving counseling for antenatal diagnosis of agenesis of the septum pellucidum. VINALS*, P. RUIZ*†, F. CORREA‡ and P. GONC¸ ALVES PEREIRA§ Ultrasound Obstet Gynecol 2016; 48: 733–738*Centro AGB Ultrasonographic, Clinica Sanatorio Aleman Facultad de Medicina, Universidad de Concepcion ´ on, Concepcion ´ on, Chile; †Hospital Costa del Sol, Marbella, Spain; ‡Fetal and Neonatal Ultrasound Department, Hospital Fernando Fonseca, Lisbon, Portugal; §Neuroradiology Department, Hospital Lusardi’s, Lisbon, Portugal

13. Ultrasound Nomograms of the Fetal Optic Nerve Sheath Diameter Krajden Haratz et al Ultraschall Med 2018 Jul 4.

14. E.S. Pickup et al Isolated Absent Septum Pellucidum: A Retrospective Study of Fetal Diagnosis and Postnatal Outcomes. Pediatr Neurol. 2022 Aug 5; 136:8-14).

15. Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse Mehul T. Dattani, Juan-Pedro Martinez-Barbera, Nature Genetics volume 19, pages 125–133 (1998)

16. Novel Genetic Diagnoses in Septo-Optic Dysplasia Linda M Reis 1, Sarah Seese 1, Mohit Maheshwari 2, Donald Basel 1, LuAnn Weik 1, Julie McCarrier 1, University Of Washington Center For Mendelian Genomics 3, Elena V Semina Genes (Basel). 2022 Jun 28;13(7):1165).

17. Prenatal diagnosis of absence of the septum pellucidum associated with septo-optic dysplasia Ultrasound Obstet Gynecol 2005; 25: 73–75C. LEPINARD*, R. COUTANT†, F. BOUSSION*, D. LOISEL‡, B. DELORME‡, F. BIQUARD*, D. BONNEAU§, A. GUICHET§ and P. DESCAMPS*Departments of *Obstetrics and Gynecology, †Pediatrics, ‡Radiology and §Medical Genetics, CHU Angers, France
         
 
 

Q04.4

Two elements that can make one suspect SOD are accessible on ultrasound or MRI: the anomaly of the leaflets and the anomaly of the optic tract:

Absence of the septum pellucidum cavum leaflets is identified in many brain abnormalities, including primary brain disorders, such as holoprosencephaly (with septal agenesis), agenesis/dysgenesis of the corpus callosum (with widely separated or mispositioned septal leaflets), ballooning of the cavum septi pellucidi (with lateral displacement of the septal laminae, as has been reported in the 22q11 microdeletion syndrome), hydrocephalus (with displacement of the medial laminae and small or collapsed cavum), as well as secondary disruptive or compressive processes (hydrocephalus, hydranencephaly, and schizencephaly/porencephaly). (1)

Therefore, ASP is defined as isolated when there are no other major cerebral or extracerebral abnormalities and when the size of the lateral cerebral ventricle is <15 mm. ASP is defined as partial if only one of the two leaflets was absent and as complete if both leaflets were absent. (3) 

In the presence of this first sign, the evaluation of the optic tract seems to be a means to improve the diagnostic suspicion of SOD and there have been many studies published supporting the role of ultrasound in evaluation of this structure.

In 2007 Bault and Salomon developed reference values for the measurements of the posterior branches of the optic chiasm, they used 3D ultrasound (4,5). In 2016 Bault suggested that measurements are easier using only the volume contrast imaging (VCI) mode in an axial plane (6). In 2016 Paladini et al confirmed that 2D ultrasound is as reliable as 3D ultrasound for visualization of the optic chiasm: for 3D ultrasound they used an axial plane with VCI and showed that measurements at the decussation level are more reproducible than those in the optic tracts, with low intra- and interoperator variability (7). Vinals et al in 2016 performed these decussation measurements in a 2D coronal plane by transvaginal neurosonography, although the  technique was limited  by fetal presentation (8).

The results of various studies have shown that these measurements of the the chiasma decussation, and or a short segment of the optic tracks may raise the suspicion towards the diagnosis of SOD, however the results remain variable from one study to another: for Bault et al (2011) 1/13 fetuses with hypoplastic posterior branches were blind and probably had SOD (Ref). For Vignals et al (2016) 3/8 fetuses had SOD with an unusually small optic chiasm, but also schizencephaly, which cannot be considered purely septal agenesis. For Di Pasquo et al (2021) in a review of 78 fetuses, it was shown that the diagnosis of isolated SOD on prenatal imaging (US and MRI) can be considered definitive in 86% of cases, fetuses with ASP have a 19% overall risk of SOD, with 40% of the additional abnormalities detected postnatally being optic nerve anomalies. For Shinar et al (2020), the study showed that 18/214 fetuses with ASP are suspected of SOD, 12 elected to continue the pregnancy and gave birth to a live infant, 5 had postnatally confirmed SOD, and 2 of these had additional MRI abnormalities such as optic nerve hypoplasia. 

Haratz et al. showed the sonographic assessment of the optic nerve and sheath diameter, along its retrobulbar section in cases of increased intracranial pressure. Although originally not aimed for the diagnosis of SOD, this approach may provide additional tool when assessing ASP and SOD (K Haratz et al.  UOG  2011; 38: 646–651)

The experience of the operator, the type of prenatal evaluation, and the technical equipment used for fetal imaging can probably explain the great heterogeneity of prenatal and postnatal results. The best results now seem to be obtained by US, probably because of the higher resolution of the images.

It should be noted that it is not possible today to evaluate the endocrine function of the fetus. Only one study: Lepinard (2005) suspected a SOD from a very low estriol maternal serum and urine level suggesting a fetal ACTH insufficiency (9).

Optic nerve measurements need to be improved using both US and MRI to enhance the prenatal diagnosis of SOD and to facilitate prenatal counseling. However, today, the final diagnosis can only be confirmed after birth, when pituitary function tests and ophthalmologic evaluations can be performed.

Prenatal counseling of parents of a fetus with suspected ASP is a difficult exercise in fetal medicine. Indeed, in most cases (3), isolated agenesis of the septum pellucidum has a favorable prognosis, however in case of SOD: visual or endocrine anomalies, and neurodevelopmental delay are responsible for a poor prognosis.

In most cases SOD is a rare anomaly ,sporadic in occurrence, with etiology llinked to multifactorial risk factors and hence  low recurrence risk. Recently a genetic association has been found in  a cohort of families with de novo variants in the SOX2, SHH and ARID1A genes, suggesting that genetic testing may be warranted when this diagnosis is suspected, particularly if associated anomlies are detected (10).  

1-Long-term postnatal outcome of fetuses with prenatallysuspected septo-optic dysplasia S. SHINAR1, S. BLASER2, D. CHITAYAT3,4, T. SELVANATHAN5, V. CHAU5, P. SHANNON6, S. AGRAWAL1, G. RYAN1, V. PRUTHI1, S. P. MILLER5, P. KRISHNAN2 and T. VAN MIEGHEM Ultrasound Obstet Gynecol 2020; 56: 371–377

1Ontario Fetal Centre, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada; 2Department of Diagnostic Imaging, Hospital for Sick Children, Department of Medical Imaging, University of Toronto, Toronto, ON, Canada; 3Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada; 4Division of Clinical and Metabolic Genetics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada; 5Department of Pediatrics, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada; 6Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada

2-Role of three-dimensional ultrasound measurement of the optic tract in fetuses with agenesis of the septum pellucidum

J. P. BAULT*†‡, L. J. SALOMON†‡, L. GUIBAUD§ and R. ACHIRON¶

Ultrasound Obstet Gynecol 2011 ; 37 : 570–575 

*Centre d’Echographies Ambroise Pare Les Mureaux, CHI Poissy Saint-Germain, Yvelines, France; †Maternité Necker-Enfants Malades, PHP, Université Paris Descartes, Paris, France; ‡SFAPE: Société Pour l’Amélioration des Pratiques en Echographie, Paris, France;§Imagerie Pédiatrique et Fœtale, Hˆ hôpital Femme Mère Enfant, Université Claude Bernard Lyon I, Lyon Bron, France; ¶Department of Obstetrics and Gynecology, Sheba Medical Center, Sackler Scholl of Medicine, Tel Aviv University, Tel Aviv, Israël

3-Prenatal diagnosis and outcome of fetuses with isolated

agenesis of septum pellucidum: cohort study and

meta-analysis E. DI PASQUO1, M. KULEVA2,3, C. ARTHUIS3, G. MORGANELLI1,4, F. ORMITTI5, A.-E. MILLISCHER6, D. GREVENT6, Y. VILLE3, T. GHI1,4# and L. J. SALOMON3# Ultrasound Obstet Gynecol 2022; 59: 153–161

1Department of Obstetrics and Gynecology, University Hospital of Parma, Parma, Italy; 2Department of Obstetrics, Hopital

Intercommunal de Montreuil, Montreuil, France; 3Department of Obstetrics and Fetal Medicine, Hopital Necker-Enfants Malades, Assistance Publique-Hopitaux de Paris, Paris Descartes University, Paris, France; 4Department of Medicine and Surgery, Obstetrics and Gynecology Unit, University of Parma, Parma, Italy; 5Department of Radiology, University Hospital of Parma, Parma, Italy; 6Departmentof Pediatric Radiology, Hopital Necker-Enfants Malades, APHP, Universite Paris Descartes, Paris, France

4- Visualization of the fetal optic chiasma using three-dimensional ultrasound imaging. BAULT JP. Ultrasound Obstet Gynecol

2006; 28: 862–864.

5- P38.13: fetal optic chiasm measurements: reference range at 22–36 weeks of gestation. BAULT JP, SALOMON LJ. Ultrasound Obstet

Gynecol 2007; 30: 596.

6-OP23.10: Fetal optic chiasm measurements: a simpler way! J. Bault Ultrasound in Obstetrics & Gynecology 2016;48(Suppl. 1): 51 – 166.

7-Assessment of fetal optic chiasm: an echo anatomic and reproducibility study. PALADINI*, R. BIRNBAUM*, G. DONARINI*, I. MAFFEO* and E. FULCHERI† Ultrasound Obstet Gynecol 2016; 48: 727–732

*Fetal Medicine and Surgery Unit, Istituto G. Gaslini, Genoa, Italy; †Fetopathology Unit, Istituto G. Gaslini, Genoa, Italy

8-Two-dimensional visualization and measurement of the fetal optic chiasm: improving counseling for antenatal diagnosis of agenesis of the septum pellucidum. VINALS*, P. RUIZ*†, F. CORREA‡ and P. GONC¸ ALVES PEREIRA§ Ultrasound Obstet Gynecol 2016; 48: 733–738

*Centro AGB Ultrasonographic, Clinica Sanatorio Aleman Facultad de Medicina, Universidad de Concepcion ´ on, Concepcion ´ on, Chile; †Hospital Costa del Sol, Marbella, Spain; ‡Fetal and Neonatal Ultrasound Department, Hospital Fernando Fonseca, Lisbon, Portugal; §Neuroradiology Department, Hospital Lusardi’s, Lisbon, Portugal

9-Prenatal diagnosis of absence of the septum pellucidum

associated with septo-optic dysplasia Ultrasound Obstet Gynecol 2005; 25: 73–75C. LEPINARD*, R. COUTANT†, F. BOUSSION*, D. LOISEL‡, B. DELORME‡, F. BIQUARD*, D. BONNEAU§, A. GUICHET§ and P. DESCAMPS*

Departments of *Obstetrics and Gynecology, †Pediatrics, ‡Radiology and §Medical Genetics, CHU Angers, France

10.Novel Genetic Diagnoses in Septo-Optic Dysplasia; Genes 2022, 13, 1165

Reis L, Seese S, Maheshwari M, Basel D, Weik L, McCarrier J,University of Washington Center for Mendelian Genetics, Semina E.

Please note that the maximum upload size is 5MB, and larger images and video clips can be sent to [email protected].